A Study of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies (ARC-27)

A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

The primary purpose of this study is to assess the safety and tolerability of AB801 in participants with advanced malignancies, and to determine a recommended AB801 dose for expansion.

Study Overview

• Status: Recruiting
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Zimberelimab; Drug: AB801

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +1-510-462-3330; Email: ClinicalTrials@arcusbio.com

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Start Midwest
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START - South Texas Accelerated Research Theraputics, LLC.
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Monotherapy-specific criteria for dose escalation cohorts:

  • Participants may have cytologically or pathologically confirmed non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC), breast, ovarian, renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), or bladder carcinoma that has progressed or was non-responsive to available therapies with no standard of care (SOC) options, or for whom standard therapy has proven ineffective, intolerable, or considered inappropriate; or for whom a clinical study of an investigational agent is a recognized SOC.

• Disease-specific criteria for dose-expansion Cohort 1 (STK11m [mutated or deleted] NSCLC):

  • Cytologically or pathologically confirmed locally advanced unresectable or metastatic (Stage IIIB-IV per American Joint Committee on Cancer [AJCC] version 8) non-squamous NSCLC with documented mutation or deletion in the STK11 gene.
  • Negative for actionable mutations including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), mesenchymal-epithelial transition factor (C-MET) or ret proto-oncogene (RET). Mixed small-cell lung carcinoma (SCLC) and squamous NSCLC histology is not permitted.
  • Previously treated in the unresectable locally advanced or metastatic setting with a platinum-containing chemotherapy and programmed cell death ligand-1 (PD-L1) inhibitor.

• Disease-specific criteria for dose-expansion Cohort 2 (NSCLC):

  • Cytologically or pathologically confirmed locally advanced unresectable or metastatic (Stage IIIB-IV per American Joint Committee on Cancer version 8) non-squamous NSCLC negative for actionable mutations in EGFR, ALK, ROS1, NTRK, C-MET, or RET. Mixed SCLC and squamous NSCLC histology is not permitted.
  • Previously treated in the unresectable locally advanced or metastatic setting with a platinum-containing chemotherapy and PD-(L)-1inhibitor.
• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance (Version 1.1) (Section 1.1). The measurable lesion must be outside of a radiation field if the participant received prior radiation unless discussed and approved by the study physician.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Key Exclusion Criteria:

• Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
• Underlying medical conditions or adverse events that, in the physician or sponsor's opinion, will make the administration of investigational products hazardous.
• Prolonged QT interval defined as mean corrected QT interval (QTc) ≥ 450 milliseconds (ms).
• Any active or documented history of autoimmune disease, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment.
• Treatment with systemic immunosuppressive medication (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-α agents) administered within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort 1 - AB801 Dose Level 1; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 2 - AB801 Dose Level 2; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 3 - AB801 Dose Level 3; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 4 - AB801 Dose Level 4; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 5 - AB801 Dose Level 5; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Escalation Cohort 6 - AB801 Dose Level 6; Participants will receive AB801 orally daily	Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Expansion Cohort 1- AB801 + Zimberelimab + Docetaxel; Participants with NSCLC with known mutation or deletion of serine/threonine kinase 11 gene will receive AB801 orally in combination with zimberelimab and docetaxel administered via intravenous (IV) infusion	Drug: Docetaxel; Administered as specified in the treatment arm; Drug: Zimberelimab; Administered as specified in the treatment arm; Drug: AB801; Administered as specified in the treatment arm
Experimental: Dose Expansion Cohort 2 - AB801 + Docetaxel; Participants with NSCLC will receive AB801 orally in combination with docetaxel IV infusion	Drug: Docetaxel; Administered as specified in the treatment arm; Drug: AB801; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	Up to 2 years
Dose Escalation Cohorts: Number of Participants With Dose-Limiting Toxicities (DLTs)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Drug Concentration-Time Curve (AUC)	Predose, Up to 8 hours postdose
Maximum Concentration (Cmax) in Plasma	Predose, Up to 8 hours postdose
Time to Maximum Concentration (Tmax) in Plasma	Predose, Up to 8 hours postdose
Objective response rate (ORR) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Up to 2 years
Dose Expansion Cohorts: Duration of Response (DOR) as Assessed per RECIST v1.1	Up to 2 years

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Investigators: Study Director: Medical Director, Arcus Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 1, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer (NSCLC); AB801
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: ARC-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No